Cardiac defects are the most frequent occuring major birth defect. This study focuses on the primordium of membranous septa and valves called cushion tissue (CT). Maldevelopment of CT accounts for 95% of congenital heart disease. The overall objective is to test whether the composition and spatial interrelationships of embryonic cardiac extracellular macromolecules mediate genetic expression in CT morphogenesis and if matrix alternations constitute a principle underlying factor predisposing an embryo to valvular and septal defects. In this study the glycosaminoglycans (GAG) and glycoproteins (GP) of any differences with those identified in mural (non-CT forming areas, e.g., ventricle). The capacity of AV or normal GAG or GP moieties (individually or synergistically to influence CT morphogenesis will be tested on artificial reconstructions of the in situ microenvironment. Preliminary studies have shown that the major events in early CT morphogenesis can be duplicated in vitro using 3-dimensional, low-density, hydrated lattices of repolymerized collagen. Parameters of analysis will include effects on (1) surface phenomena (lectin binding, clustering and number of intramembranous particles, membrane electrical potential, collagen binding sites); (2) migratory behavior (number and size of motility appendages, rate of translocation, cell aggregation, etc.); (3) matrix secretion; (4) intracellular calcium concentrations, and (5) ultrastructural phenotype. Other in vitro reconstitutional experiments designed to test potential GAG and GP inductive effects will involve (1) adding myocardial aggregates (active in producing the in situ premigratory GAG and GP) to the base of 3-D gels; (2) substituting 3-D gels with isolated native matrix (cardiac jelly) which has been experimentally modified in composition or intermolecular associations and (3) culturing CT progenitor (endocardium) in chemotactic chambers containing various GAG and GP. The data, mostly expressed quantitatively, should reveal any "inductive" or regulatory influences of specific GAG or GP upon the development of valvular and septal primordia.